We propose to use prospectively collected dietary data and frozen plasma and DNA specimens to address a series of hypotheses regarding major cancers and their premalignant precursors in men and women. The cancers and precursors that we will study are primarily those of the breast, colon and rectum, prostate, and lung. Project 1 will extend the biennial follow-up of 51,529 men who completed an extensive dietary questionnaire first in 1986 and again in 1990 and 1994 (The Health Professionals Follow-up Study, HPFS). Follow-up has been high and the study has already contributed substantially to information on diet and cancers of the prostate and colon. In the proposed continuation, we will extend and refine observations from our first eight years of follow-up and also address several new hypotheses using dietary, biochemical, and molecular data. Project 2 assesses diet in relation to newly diagnosed cases of adenomatous large bowel polyps in the HPFS and among 90,000 women in the Nurses Health Study I who completed dietary questionnaires in 1980,1984, 1986, 1990, and 1994. Important findings have already been published on dietary fiber, fat, red meat, folate, methionine, and alcohol. These findings and a series of new hypotheses will be evaluated with the extended follow-up, which will provide a total of 3,115 newly diagnosed adenomas. Project 3 evaluates histopathologic characteristics of benign breast disease biopsies between 1991 and 1997 among women enrolled in the Nurses Health Study II, and will analyze risk in relation to dietary data collected in 1991. Project 4 pools data from all major prospective studies of diet and cancer. Precise and unique information has already been obtained regarding the relation of dietary-fat intake to breast cancer. The extended follow- up will provide powerful data on diet and cancers of the breast and colon, and renal cell cancer and will allow a re-examination of potentially important new findings regarding dietary fat and breast cancer. Through these interrelated prospective studies, we anticipate a substantial increase in our understanding of, and thus the ability to prevent, the most important cancers of men and women.